(4R)-4-phenyl-1,3-oxazolidin-2-one → 3-[(2-fluorophenyl)-acetyl]-4(R)-phenyl-2-oxazolidinone

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반응 단계

A solution of 46.0 g of (R)-4-phenyl-2-oxazolidinone in 300 g (338 mL) of peroxide-free tetrahydrofuran is cooled to −5 to 0° C. (bath temperature −10 to −5° C.) over a period of 15 minutes. 145.2 g (166.8 mL) of 25% w/w potassium t-amylate/toluene solution is added over a period of 25 minutes while maintaining an internal temperature below 0° C. The reaction mixture is warmed to 20±5° C. within 1 hour and stirred at this temperature for 2.5-3 hours. The mixture is cooled to −15 to −5° C. over a period of 30 minutes, and crude 2-fluorobenzenacetyl chloride (obtained above) is added over a period of 45 minutes while maintaining an internal temperature below −5° C. (bath temperature −15 to −10° C.). After the addition is completed, the mixture is warmed to 20±5° C. over a period of 1 hour, and diluted with 100 mL of toluene. This is added to 500 mL of saturated citric acid monosodium salt solution (100 g in 450 g of water) and the mixture is stirred for 5 minutes. The organic layer is separated, and washed with 1 L of sodium chloride solution (200 g in 800 g of water) in two equal portions of 500 mL each. The solution is concentrated to dryness under reduced pressure (66-76 mm Hg, bath temperature 65-70° C.) to obtain 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone as a semi-solid. The semi-solid is suspended in 450 mL of t-butyl methyl ether and the mixture is heated to reflux (53-58° C.) to obtain a solution; 225 mL of t-butyl methyl ether is then distilled off at atmospheric pressure (bath temperature 60-65° C.). The resulting mixture is cooled to 20-25° C., and stirred at this temperature for 16 hours, then cooled to −5 to 0° C. and stirred at this temperature for additional 2 hours and filtered. The resulting solid is dried under vacuum (66-76 mm Hg) at 45-50° C. for 12 hours to obtain 3-[2-(2-fluorophenyl)-1-oxoethyl]-4(R)-phenyl-2-oxazolidinone as a white crystalline solid.

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